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基因研究结果揭示骨髓衰竭的原因

By LabMedica International staff writers
Posted on 20 Mar 2014
研究人员发现了骨髓衰竭患者的一个新的基因缺陷,它可能揭示深层原因。

范可尼贫血、先天性角化不全症和再生障碍性贫血等骨髓衰竭综合征是一组各不相同的致命疾病,特征是骨髓不能制造足够数量的成熟血细胞。

英国伦敦玛丽王后大学的科学家们及其同行从骨髓衰竭病例库里选了三例基因特征指标不明的病例。他们进行了外显子组测序,目标是发现一个常见基因的变异。这三个病例有三系——红细胞、髓细胞和巨核细胞——骨髓衰竭,它们来自同血缘的家族。三个病例都有以学习功能障碍为特征的发育延迟,其中两个病例还有小头畸形。

取得三名患者的外周血样本并提取DNA。研究使用了多种其它技术,如组织学与免疫组化、免疫细胞化学、成像与共定位检查、实时聚合酶链反应(PCR)与免疫印迹密度测定以及小干扰核糖核酸RNA (siRNA)检查。为评估活性氧(ROS)的基础水平,用ROS标记物二氢乙锭标记细胞,通过流式细胞术测量荧光。用德国奥滕贝格BMG Labtech公司的FLUROstar Optima酶标仪测量处理后ROS荧光的实时变化。

外显子组测序揭示,所研究的三例骨髓衰竭和发育延迟病例中的两例ERCC6L2基因有纯合截断突变。ERCC6L2基因的这一突变将一种独特的骨髓衰竭综合征与DNA修复和线粒体功能联系在一起。上述结果意味着现在可能对这些家庭实行可靠的基因检验,包括产前检验,并得到准确的诊断结果。长远来看,随着研究的深入,上述发现可能有助于开发新疗法治疗这一特殊的基因缺陷。

该研究的论文发表于2014年2月6日的《美国人类遗传学杂志》(American Journal of Human Genetics)。资深作者、儿科与儿童健康系教授Inderjeet Dokal大夫说:“新的DNA测序技术使我们能够发现和定义一种新的基因缺陷,它导致一类特殊的骨髓衰竭。这是一项有希望的发现,我们希望有一天它能引导我们发现这种基因缺陷的有效疗法。现在临床医师治疗骨髓衰竭时应该将对这一基因的分析纳入研究。”

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